Considerable progress has been made in developing nucleosides with anticancer and/or antiviral activity by modifying the base portion of a nucleoside. For example, 3-deazaadenosine, a potent inhibitor of adenosylhomocysteine hydrolase, has been shown to have significant activity against herpes simplex virus type-1, human immunodeficiency virus and oncogenic DNA viruses. Bodner, A. J.; Cantoni, G. L.; Chiang, P. K. Biochem. Biophys. Res. Commun. 1981 98, 476-481. Flexner, C. W.; Hildreth, J. E.; Kuncl, R. W.; Drachman, D. B. Lancet 1992 339, 438. Bader, J. P.; Brown, N. R.; Chiang, P. K.; Cantoni, G. L. Virology 1978 89, 494-505. Chiang, P. K.; Cantoni, G. L.; Bader, J. P.; Shannon, W. M.; Thomas, H. J.; Montgomery, J. A. Biochem. Biophys. Res. Commun. 1978 82 417-423. 3-Deazaguanosine has been reported to possess broad spectrum antiviral activity against a variety of DNA and RNA viruses, as well as antitumor activity against the L1210 leukemia and several mammary adenocarcinomas in mice. Allen, L. B.; Huffman, J. H.; Cook, P. D.; Meyer, R. B., Jr.; Robins, R. K.; Sidwell, R. W. Antimicrob. Agents Chemother. 1977 12, 114-119. Saunders, P. P.; Chao, L. Y.; Loo, T. L.; Robins, R. K. Biochem. Pharmacol. 1981 30, 2374-2376. Revankar, G. R.; Gupta, P. K.; Adams, A. D.; Dalley, N. K.; McKernan, P. A.; Cook, P. D.; Canonico, P. G.; Robins, R. K. J. Med. Chem., 1984 27, 1389-1396.
Certain 2-halogen-substituted purine nucleosides have exhibited cytotoxicity in vitro and anticancer activity in vivo. Carson, D. A.; Wasson, D. B.; Kaye, J.; Ullman, B.; Martin, D. W., Jr.; Robins, R. K.; Montgomery, J. A. Proc. Natl. Acad. Sci. USA 1980 77, 6865-6869. Hutton, J. J.; Von Hoff, D. D.; Kuhn, J.; Phillips, J.; Hersh, M.; Clark, G. Cancer Res. 1984 44, 4183-4186. Secrist, J. A., III; Shortnacy, A. T.; Montgomery, J. A. J. Med. Chem. 1988 31, 405-410. Montgomery, J. A.; Shortnacy-Fowler, A. T.; Clayton, S. D.; Riordan, J. M.; Secrist, J. A., III. J. Med. Chem. 1992 35, 397-401. Among these analogues, Fludarabine phosphate (9-β-D-arabinofuranosyl-2-fluoroadenine 5′-O-phosphate) and Cladribine (2-chloro-2′-deoxy-β-D-adenosine) are currently used as anticancer agents.
However, notwithstanding the progress that has been made in identifying nucleosides having anticancer and/or antiviral activity, the need exists for biologically-active nucleosides that exhibit a wide range of antiviral and/or anticancer properties and that may be employed in antiviral and anticancer pharmaceutical compositions. Such nucleosides must be safe and well-tolerated and be suitable for use in numerous pharmaceutical dosage forms and routes of administration. Preferably, such nucleosides would exhibit both antineoplastic and antiviral activity upon administration to a patient in need, and would also be useful in treating bacterial infections such as tuberculosis and associated viral infections such as AIDS.